ArticleProceedings of the National Academy of Sciences of the United States of America2021
The K63 deubiquitinase CYLD modulates autism-like behaviors and hippocampal plasticity by regulating autophagy and mTOR signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- CYLD-mediated lysine63 deubiquitination regulates synaptic transmission and autophagy to mitigate age-related sequelae.Nature communications · 2026Article
- The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.Genomic psychiatry : advancing science from genes to society · 2025Article
- The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity.bioRxiv : the preprint server for biology · 2025Article
- Cypin regulates K63-linked polyubiquitination to shape synaptic content.Science advances · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Auts2 enhances neurogenesis and promotes expansion of the cerebral cortex.Journal of advanced research · 2025Article
- Role of CYLD in brain physiology and pathology.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Article
- Constitutive expression of the deubiquitinating enzyme CYLD does not affect microglia phenotype or function in homeostasis and neuroinflammation.Journal of molecular medicine (Berlin, Germany) · 2024Article
- The role of deubiquitinases in cardiac disease.Expert reviews in molecular medicine · 2024Review
- MALT-1 shortens lifespan by inhibiting autophagy in the intestine ofAutophagy reports · 2023Article
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- Biocytin-Labeling in Whole-Cell Recording: Electrophysiological and Morphological Properties of Pyramidal Neurons in CYLD-Deficient Mice.Molecules (Basel, Switzerland) · 2023Article
- The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.International journal of molecular sciences · 2023Review
- Neural mechanism underlies CYLD modulation of morphology and synaptic function of medium spiny neurons in dorsolateral striatum.Frontiers in molecular neuroscience · 2023Article
- Trimetazidine mitigates high glucose-induced retinal endothelial dysfunction by inhibiting PI3K/Akt/mTOR pathway-mediated autophagy.Bioengineered · 2022Article
- IKK-mediated CYLD phosphorylation and cellular redox activity.Molecular medicine (Cambridge, Mass.) · 2022Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron spine numbers. By providing evidence that CYLD can modulate mechanistic target of rapamycin (mTOR) signaling and autophagy at the synapse, we propose that synaptic K63-linked ubiquitination processes could be fundamental in understanding the pathomechanisms underlying autism spectrum disorder.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.